Biodegradable synthetic polymers offer a number of advantages over other materials in various biological applications including tissue repair. For example, in relation to the development of scaffolds in tissue engineering, the key advantages include the ability to tailor mechanical properties and degradation kinetics to suit various applications. The simple and routine fabrication of scaffolds with a size and shape similar to organs or parts of organs would, for example, help tissue engineering technology to develop such organs in vivo or in vitro using bioreactors. Likewise, scaffolds with appropriate mechanical properties can be fabricated and implanted in the body to help repair damaged tissues such as those in coronary arteries and other blood vessels. For example, biodegradable scaffolds fabricated as coronary stents can support the vessel during the healing process and degrade and be released from the body after the vessel is repaired.
Synthetic polymers are also attractive in tissue engineering applications because they can be fabricated into various shapes with desired pore morphologic features conducive to tissue in-growth. Furthermore, polymers can be designed with chemical functional groups that can, for example, induce tissue in-growth, or be utilised to adapt the polymers to the application in question.
A vast majority of biodegradable polymers studied in these fields belong to the polyester family. Among these, poly(α-hydroxy acids) such as poly(glycolic acid), poly(lactic acid) and a range of their copolymers have historically comprised the bulk of published material on biodegradable polyesters and have a long history of use as synthetic biodegradable materials in a number of clinical applications. Poly(glycolic acid), poly(lactic acid) and their copolymers, poly-p-dioxanone, and copolymers of trimethylene carbonate and glycolide have been the most widely used as scaffolds. Their major applications include as resorbable sutures, drug delivery systems and orthopaedic fixation devices such as pins, rods and screws. Among the families of synthetic polymers, the polyesters have been attractive for these applications because of (i) their ease of degradation by hydrolysis of the ester linkage, (ii) degradation products are resorbed through the metabolic pathways in some cases and (iii) the potential to tailor the structure to alter degradation rates.
The recent interest in finding tissue-engineered solutions to repair damaged tissues and organs due to injury/disease has led to the development of new degradable polymers that meet a number of demanding requirements. These requirements range from the ability of the polymer scaffold to provide mechanical support during tissue growth and gradual degradation to biocompatible products, to more demanding requirements such as the ability to incorporate drugs, cells and growth factors, for example, and provide cell-conductive and inductive environments as well as promotion of the healing process. Drugs to suppress inflammatory response and promote the healing process can be incorporated within the biodegradable polymer scaffold or as a drug-eluting coating on the surface of the scaffold. Many of the currently available degradable polymers do not meet all of the requirements to be used in such applications. Most biodegradable polymers in the polyester and ester family, for example, are hydrophobic in nature and as such, only a limited number of drugs can be incorporated into such polymers.
In particular, biodegradable synthetic polymers with appropriate mechanical properties are sought after for the development of biodegradable stents and stent coatings for the treatment of coronary artery disease by percutaneous intervention. Stents provide mechanical support for the vessel and keep the lumen open to its normal diameter while tissue growth takes place to repair the affected vessel wall. Current stents are fabricated using metals such as stainless steel or nickel-titanium alloys, and once deployed these stents remain permanently within the vessel. Biodegradable polymers have the advantage of being removable from the vessel through polymer degradation and resorption once the vessel is repaired. This leaves the repaired vessel free of foreign material and allows re-stenting if needed in the future. Biodegradable polymers can also be useful in delivering drugs such as sirolimus, everolimus and paclitaxel D-actinomycin, all of which help to inhibit the formation of neointimal hyperplasia by suppression of platelet activation, suppression of inflammatory response, and promotion of the healing.
Scaffolds made from synthetic and natural polymers, and ceramics have been investigated extensively for orthopaedic repair. The use of scaffolds has advantages such as the ability to generate desired pore structures and the ability to match size, shape and mechanical properties to suit a variety of applications. However, shaping these scaffolds to fit cavities or defects with complicated geometries, to bond to bone tissue, and to incorporate cells, drugs and growth factors, and the requirements of open surgery are a few major disadvantages of the use of known scaffold materials.
The most common synthetic polymers used in fabricating scaffolds for growing cells and for biodegradable stents and stent coatings belong to the polyester family. For example, poly(glycolic acid) and poly(lactic acid) have been the most commonly used polymers because of their relative ease of degradation under hydrolytic conditions and the resorption of the degradation products into the body. However, these polymers have a number of disadvantages, including rapid loss of mechanical properties, long degradation times, difficulty in processing, and the acidity of degradation products resulting in tissue necrosis. These polymers, when used in biodegradable stents, have to be heated during the deployment process to temperatures as high as 70° C. which can cause cell damage.
Common methods that are currently employed for the synthesis of three dimensional biodegradable tissue engineering scaffolds include: porogen leaching, gas foaming, phase separation and the use of non-woven mesh. All of these methods have disadvantages including that:                they require a mould to shape the scaffold—this is costly and can only produce a single shape;        these methods offer little or no control over the orientation of the pores and degree of interconnectivity;        usually a polymer skin forms on a moulded scaffold (even if it is porous) which can require extensive post-synthesis treatment; and        some of the methods of scaffold fabrication such as phase separation and porogen leaching often involve the use of toxic organic solvents which is undesirable.        
A controlled rapid prototyping method can address these problems. The shape of the mould can be quickly altered by computer design, the direction and degree of porosity can be specified to exact levels, a polymer skin is not formed in production, and the process is solvent free. When fabricating scaffolds such as stents for example, the process can be modified to deposit a grid like layout with polymer strands to dimensions and patterns specific to the stent design. The grid structure can then be used to fabricate the stent. Alternatively, the grid structure could be deposited on a rotating mandrel to fabricate the stent in one operation.
There are a number of different rapid prototyping machines available in the marketplace.
Synthetic polymers that can be used in such rapid prototyping apparatus need to meet specific property requirements which include melt processing characteristics, mechanical properties and other properties. For example, in fused deposition modelling (FDM) applications, the polymer must be able to be melt-processed into a filament of appropriate diameter for the rate of extrusion of the particular FDM apparatus.
Most synthetic biodegradable polymers do not meet the requisite property requirements. A review of the literature indicates that among the biodegradable polymers only poly-(ε-caprolactone) meets some of the requirements. Hutmacher et al at the National University of Singapore (Biomaterials, 24: 4445-4448, 2003) have reported the use of poly-(ε-caprolactone) (PCL) (MW 80,000) to fabricate tissue engineering scaffolds. They have also reported the use of hydroxyapatite as a filler (Schantz et al, Materials Science and Engineering 20: 9-17, 2002) in PCL to fabricate 3D constructs for bone tissue applications. A report by a group from the University of Nottingham (Christian et al, Composites: Part A, 32: 969-976, 2001), discusses PCL impregnated with long glass fibre in a MDM (Material Deposition Modelling) process to fabricate scaffolds. Commercially the market for biodegradable structures with interconnected pores is very large and growing rapidly. One product available is Degrapol® foam which is based on polyurethanes but they have much less control of the degree of porosity, orientation of pores and pore morphology, and it is available only as small foam discs (except on special order).
Polymers that can be used to fabricate biodegradable scaffolds using rapid prototyping techniques such as FDM need to meet a set of criteria including that:                the polymer must be thermoplastic;        the polymer must be extrudable;        the filament must be mechanically stiff and have a low melt viscosity (a high Melt Flow Index); and        the polymer must be biodegradable and biocompatible (eg. contain groups that are liable to hydrolyse and have degradation products that are non-toxic).        
In short, the use of rapid prototyping machines to make porous, highly controlled and interconnected tissue engineering structures requires a complex combination of various techniques including polymer chemistry, polymer processing, rapid prototyping and tissue engineering and, accordingly, is particularly complex.
Accordingly, there is a need for biocompatible and biodegradable polymers that can be processed using methods including rapid prototyping as well as thermal and solvent based methods to fabricate scaffolds and coatings for various biomedical applications including tissue engineering.
It is thus one object of this invention to develop polymers with properties suited to use in rapid prototyping techniques which will, in turn, enable the fabrication of three dimensional scaffolds with complicated structures for use in tissue growth and repair therapies and technologies, including the fabrication of stents, and coatings for stents useful in drug delivery.